Current treatment of inflammatory bowel disease (IBD) is of limited efficacy, as there are no entirely non-toxic pharmaceuticals that totally halt or reverse the progression of IBD. To address this need, Inotek is developing a series of novel anti-colitic agents that detoxify peroxynitrite, a potent oxidant formed in the intestinal mucosa of ulcerative colitis and Crohn?s Disease. Using a murine dextran sulfate model of enterocolitis, we have determined that our lead peroxynitrite decomposition catalyst, FP15, profoundly reduced bloody diarrhea, gross and microscopic histologic injury, lipid peroxidation, and weight loss and increased colon length and survival. In the Phase II SBIR, we intend to demonstrate that the in vivo toxicologic profile of FP15 meets FDA standards for progression to clinical studies. Specific Aim #1: Kilogram level production of FP15. Pre-clinical evaluation of FP15, including toxicology, metabolism, and pharmacokinetic studies, requires process scale-up to produce kilogram scale GLP-grade material. Specific Aim #2: Determine the in vivo pharmacokinetics, distribution, bioavailabllity, metabolism, and excretion (ADME) of FP15 in rats and canines. Specific Aim #3: Determine the biochemical, hematologic, and histopathologic toxicology profile of FP15. Definitive chronic toxicity studies wifi provide a comprehensive behavioral, biochemical, and histopathologic profile These studies will provide the foundation for clinical testing, commercial development, and first market entry of an ultrapotent peroxynitrite decomposition catalyst for therapy of IBD. PROPOSED COMMERCIAL APPLICATION: The annual domestic impact of IBD on the health care market is estimated at > $1 billion. The worldwide market in IBD (developed countries only) is four times larger. Given the absence of a specific and completely effective therapy, Inotek anticipates market acceptance to be achieved rapidly, at high levels of penetration, and with a high sustained price point ($1000 per patient per year). Estimated worldwide gross sales revenues after market entry and maturation (ca. 4 years after FDA approval) equal $800 million (anual).